Optical Coherence Tomography Reveals Longitudinal Changes in Retinal Damage Under Different Treatments for Neuromyelitis Optica Spectrum Disorder

Abstract

Background: Progressive retinal neuroaxonal damage after acute optic neuritis may occur in neuromyelitis optica spectrum disorder (NMOSD). However, it is unclear if treatments used to prevent attacks influence neurodegeneration.Objectives: We aimed to investigate retinal damage in patients treated with disease-modifying drugs in a longitudinal study.Methods: We retrospectively included 50 patients with aquaporin 4-antibody-seropositive NMOSD. Peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex (mGCC) thickness, total macular volume (TMV), and optic disc measures were acquired by spectral domain optical coherence tomography in patients treated with tocilizumab, rituximab, and azathioprine.Results: Longitudinally, in eyes with a history of ON (NMOSDON+), we observed annual thinning of mGCC [tocilizumab: −1.77 (−3.44, −0.09) μm, p = 0.041; rituximab: −2.03 (−3.58, −0.48) μm, p = 0.017; azathioprine: −1.79 (−2.22, −1.37) μm, p < 0.001], and pRNFL [tocilizumab: −2.07 (−0.75, −3.39) μm, p = 0.005; rituximab: −2.18 (−0.36, −4.00) μm, p = 0.023; azathioprine: −2.37 (−0.98, −3.75) μm, p = 0.003], reduced TMV [tocilizumab: −0.12 (−0.22, −0.01) mm3, p = 0.028; rituximab: −0.15 (−0.21, −0.08) mm3, p = 0.001; azathioprine: −0.12 (−0.20, −0.04) mm3, p = 0.006], and increased cup area [tocilizumab: 0.08 (−0.01, 0.16) mm2, p = 0.010; rituximab: 0.07 (0.01, 0.12) mm2, p = 0.019; azathioprine: 0.14 (0.02, 0.26) mm2, p = 0.023]. However, we detected no significant differences in annual changes in mGCC, pRNFL, TMV, and cup area between patients with tocilizumab, rituximab, and azathioprine in NMOSDON+ eyes. NMOSDON− eyes did not display mGCC or pRNFL thinning in patients treated with tocilizumab and rituximab. Intriguingly, we observed significant thinning of mGCC in patients treated with azathioprine compared with tocilizumab [−0.84 (−1.50, −0.18) μm vs. −0.19 (−0.87, 0.48) μm, p = 0.012] and rituximab [−0.84 (−1.50, −0.18) μm vs. −0.07 (−1.25, −2.51) μm, p = 0.015] in NMOSDON− eyes.Conclusions: This study demonstrated that retinal ganglion cell loss is independent of ON attacks in NMOSD. Tocilizumab and rituximab may delay mGCC thinning in NMOSDON− eyes compared with azathioprine.

Tocilizumab for Neuromyelitis Optica Spectrum Disorder

“…Two observational studies with a retrospective before-after design were published in 2023 23 and 2021. 22 One study 23 retrospectively collected data for NMOSD patients treated with TCZ and compared the changes between baseline and after treatment. This study also employed adjusted logistic regression models to identify risk factors for relapse.…”

“…This study also employed adjusted logistic regression models to identify risk factors for relapse. The second study 22 included NMOSD patients treated with TCZ, AZA, and rituximab and healthy controls. This study compared the differences between baseline and after treatment within each treatment group or across the 3 drug groups as well as the difference between NMOSD patients and the healthy controls on optical coherence tomography (OCT) measures.…”

“…Four systematic reviews, [18][19][20][21] 2 non-randomized studies, 22,23 and 1 evidence-based guideline 24 were included. Three systematic reviews [19][20][21] had broader inclusion criteria on interventions; only the subset of studies reporting on TCZ and its comparison were relevant to the current report.…”

Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives

“…GC-IPL damage on OCT spatial relationship and papillomacular bundle loss in neurodegenerative disease such as mitochondriopathy or neuroinflammmatory disease require further research to elucidate the damage in the megacellular and parvocellular layers in the lateral genicular nucleus [ 139 , 141 ]. There were no significant differences in the annual changes in mGC-IPL, pRNFL, total macular volume, and disc cup ratio in the NMOSD-ON eyes when comparing patients treated with different immunosuppressive therapies [ 142 ].…”

Anti-IL-6 therapies in central nervous system inflammatory demyelinating diseases

“…In addition, compared with steroids, tocilizumab treatment led to a significantly lower ARR and risk of relapse ( 54 ). A longitudinal study investigated retinal damage in 50 patients with NMOSD who received disease-modifying drugs and reported that, compared with AZA, tocilizumab and rituximab could delay macular ganglion cell complex thinning in the eyes of patients without a history of optic neuritis ( 55 ).…”